Paraquat, a widely used herbicide, is toxic to the lungs of man and experimental animals. No antidote is currently available for the treatment of paraquat poisoning. In this proposal a plan is described for developing a rat model of paraquat lung toxicity which will mirror the pathological picture seen in man. Using this model, the mechanisms of paraquat poisoning will be investigated in an attempt to develop adequate treatment methods for paraquat poisoning. Preliminary experiments in our laboratory indicate that paraquat damages the lung via a central nervous system pathway. The finding will be explored further. The parameters of lung toxicity to be studied will be organ weight, light microscopy and hydroxyproline analysis to determine the degree of fibrosis. Tissue concentrations of paraquat will be measured to estimate the dose-response curve of paraquat in tissue. Paraquat is thought to damage tissue via a free radical mechanism. Lipoperoxides and radiomimetic effects of paraquat will be measured and correlated to lung toxicity. Antioxidants and radio-protective agents will be examined for protective effects against paraquat toxicity. Inflammation and cellular proliferation occurs in the lungs after paraquat poisoning and account for the respiratory failure seen in fetal cases. The usefulness of anti-inflammatory steroids and antimetabolites in retarding paraquat toxicity will be investigated.